LAUSR

Infantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare autosomal recessive (AR) neurodegenerative disorder which can be associated with mutations in the alsin (ALS2) gene located on chromosome 2q33. ALS2 mutations have been linked to 2 other AR neurodegenerative disorders, including juvenile primary lateral sclerosis (JPLS) and juvenile amyotrophic lateral sclerosis (JALS/ALS2). The clinical features of these 3 disorders often overlap. Although upper motor neuron involvement predominates in IAHSP and JPLS, anterior horn cells are also involved in JALS/ALS2. In IAHSP and JPLS, initial motor symptoms appear in the first 2 years of life, but the onset is between 3 to 20 years of age in JALS/ALS2. Nearly all patients with IAHSP and JPLS become wheelchair dependent by the second decade of life. IAHSP was initially reported in 1996 in 3 Kuwaiti children born of a consanguineous parentage. To date, 54 IAHSP cases have been reported, with the majority from Middle East and Mediterranean countries (Table S1). A majority of patients with IAHSP manifest only pyramidal features. Herein we describe a 19-year-old man diagnosed with IAHSP who carried a novel ALS2 gene mutation and had significant extrapyramidal and extraocular features. To the best of our knowledge, this is the first IAHSP case from India. This 19-year-old man, born of a nonconsanguineous parentage, had an uneventful perinatal history. He could sit without support at the age of 6 months, but failed to stand without support at 1 year of age, when his parents noticed stiffness involving both legs. He walked with support at 2 years of age, but could never walk without support. Truncal stiffness developed by age 4. At age 8, he became wheelchair bound and also developed stiffness in both upper extremities, affecting activities including handwriting. A hyper-nasal speech and emotional lability developed by age 10 and dysphagia by age 12. There was no bladder– bowel involvement or seizure episodes. Family history was unremarkable. Clinical examination revealed exaggerated lumbar lordosis. Although we could not do a formal cognitive assessment, it appeared preserved. He could communicate using eye movements and was able to follow commands. There were saccadic pursuits and hypometric saccades along with oculomotor apraxia (Video 1). He had minimal, spastic speech along with a